Kambo: Natural drug or potential toxic agent? A literature review of acute poisoning cases.

Kambo is the name of a natural substance derived from the glandular secretions of the amphibian Phyllomedusa bicolor, a species native to regions in South America. The communities living in these areas administer the substance generally transdermally during rituals for religious-purifying purposes, producing small skin burns. The scientific literature has reported some cases of intoxication following the use of Kambo but this aspect is still poorly understood. In fact, no shared therapy protocols exist for these events nor any real legislation on Kambo. The purpose of this work was to examine all cases of acute intoxication resulting from the administration of Kambo and published over the last 10 years, illustrating clinical signs, laboratory findings, instrumental tests, and therapy. The several cases identified in our review confirm that acute Kambo intoxication can occur, with serious and life-threatening effects. We developed a protocol aimed at the early diagnosis of cases of suspected acute intoxication by creating a treatment algorithm. The study aims to investigate the pathophysiology of these events in humans, proposing a protocol for the diagnosis and treatment of these cases that can be used by healthcare professionals.

The use of scanning electron microscopy and energy dispersive X-ray spectroscopy in a case of occupational death.

Scanning electron microscopy is a technique that provides high-resolution images at the micro- and nano-scale. The combination of scanning electron microscopy and energy dispersive X-ray spectroscopy analysis is developing fast for application in forensic science. In this work, we report a case of work-related traumatic death of a 50-year-old man. The autopsy showed cranial fractures with cerebral haemorrhage. It was more difficult to understand the accident dynamics because the body had been shifted from the accident site to mask what had really taken place. Scanning electron microscopy/energy dispersive X-ray spectroscopy was used to identify the material of the impacting tool and to establish the possible legal responsibility of the employer. In this study, we demonstrate that scanning electron microscopy/energy dispersive X-ray spectroscopy is a useful forensic tool for the analysis of biological samples. Further, for studying the lacerations on the corpse from doubtful blunt tools, scanning electron microscopy/energy dispersive X-ray spectroscopy can assist in demonstrating that the scene has been falsified, as it was in this case.

Developing and cross-validation of new equations to estimate fat mass in Italian population.

OBJECTIVE: Obesity is a global burden that involves more than 500 million people. The objective of this work is to develop and cross-validate the new sex-specific equations to estimate fat mass, based on anthropometric parameters and to compare with other equations. PATIENTS AND METHODS: We evaluated 38762 subjects by dual-energy X-ray absorptiometry (DXA) and enrolled 1434 women and 640 men, aged between 18 and 65 years. Then, we randomized 480 men and 1080 women in developing set and 160 men and 354 women in the cross-validation set. Statistical analysis as multiple regression and Bland-Altman methods were performed. RESULTS: Sex-specific equations were created based on developing set. Then, based on the cross-validating set, these equations were validated and were observed to agree with fat mass by DXA, better than other equations, such as BAI and RFM. CONCLUSIONS: These new sex-specific equations represent an easy tool, since they require only two circumferences, to be used in clinical practice. In the next future, these equations could be validated and refine on specific Italian sub-populations, divided by gender and age, such as the military.

Role of phase angle in the evaluation of effect of an immuno-enhanced formula in post-surgical cancer patients: a randomized clinical trial.

OBJECTIVE: Neoplastic disease is frequently associated with poor nutritional status or severe malnutrition. Diet and nutritional intervention are becoming increasingly important for prognosis and quality of life in cancer patients. Accessible and repeatable tools for assessing nutritional status with body composition techniques seems to be fundamental. The aim of this study was to evaluate the effects of immunonutrition on body composition parameters, inflammatory response and nutritional status in patients at stage III of head and neck squamous carcinoma (HNSCC). PATIENTS AND METHODS: In our work, 50 malnourished subjects with HNSCC staging III were recruited and treated with oral diet (OD) or enteral nutrition (EN). Patient under EN followed, for the first three days, enteral standard nutrition (ESN) and then enteral immunonutrition (EIN). Nutrition state was evaluated on days 0, 3, and 8 through body composition and biochemical analyses. RESULTS: After 8 days, the EIN treatment showed a significant improvement in phase angle, pre-albumin, retinol binding protein and transferrin compared to the OD treatment. CONCLUSIONS: Our results showed that immunonutrition treatment improves the nutritional status of neoplastic patients, supporting chemotherapy. The phase angle is not only a predictor of cancer survival, but has also proved to be useful in the surveillance of nutritional status improvement as well as biochemical indices.

The "Social-mobile autopsy": The evolution of psychological autopsy with new technologies in forensic investigations on suicide.

Suicide is a huge deal in general public health, representing the second cause of mortality in young people worldwide. The suicidal setting analysis is usually performed through psychological autopsy, a method of investigation commonly used to study what leads to suicide. Psychological autopsy, though, requires the involvement of family and friends, or the finding of a diary or a suicide note. Nowadays, this is not always possible, especially during adolescence, the more if we consider new categories of people that are more used to live in a web dimension, than in a real one. So, with the advent of a new kind of social system including the web, psychological autopsy, as we know it, is not enough to determine the setting of an event. We here report the case of a 17-year old girl who committed suicide by hanging down from her house, leaving no suicide note. We propose a new investigation method developed through the analysis of phone messages and Facebook profile in order to better reconstruct the event. Although the standing difficulties in reconsidering the intimate motivations leading to such a decision, psychological autopsy nowadays needs to consider also social networks in order to prevent similar situations and even reconstruct the psychological dimension of the fact. We propose a model of Social-mobile autopsy.

Scuba diving death: Always due to drowning? Two forensic cases and a review of the literature.

Scuba diving is an increasingly common recreational activity. We describe the physiopathology of barotrauma in two cases where death was caused by pulmonary barotrauma while diving. An inspection and autopsy were carried out in both cases. The autopsy data were supported by post-mortem radiological investigation. Histological and toxicological analyses were also carried out, and dive computer and tank manometer analysis performed. In both cases, the cause of death was attributable to arterial gas embolism, resulting from pulmonary barotrauma subsequent to pulmonary over-distension. The dive computer analysis and the tank manometer allowed us to understand what happened underwater. In our opinion, a multidisciplinary approach is crucial in order to clarify the cause of death. Some pathological conditions and risk factors should be considered before diving.

Lipid-lowering effect of bergamot polyphenolic fraction: role of pancreatic cholesterol ester hydrolase.

Bergamot polyphenolic fraction (BPF) has been shown to positively modulate several mechanisms involved in metabolic syndrome, suggesting its use in therapy. In particular, it is able to induce a significant amelioration of serum lipid profile in hyperlipemic patients at different levels. The purpose of our study was to investigate the effect of BPF on cholesterol absorption physiologically mediated by pancreatic cholesterol ester hydrolase (pCEH). An in vitro activity assay was performed to study the effect of BPF on pCEH, whereas the rate of cholesterol absorption was evaluated through in vivo studies. In particular, male, Sprague-Dawley rats (200–225 g) were fed either normal chow or chow supplemented with 0.5% cholic acid, 5.5% peanut oil, and varying amounts of cholesterol (0 to 1.5%). BPF (10 mg/Kg) was daily administrated by means of a gastric gavage to animals fed with lipid supplemented diet for 4 weeks and, at the end of the study, plasma lipids and liver cholesteryl esters were measured in all experimental groups. Our results show that BPF was able to inhibit pCEH activity and this effect was confirmed, in vivo, via detection of lymphatic cholesteryl ester in rats fed with a cholesterol-rich diet. This evidence clarifies a further mechanism responsible for the hypolipemic properties of BPF previously observed in humans, confirming its beneficial effect in the therapy of hypercholesterolemia and in the treatment of metabolic syndrome.

The probiotics in dentistry: a narrative review.

The total number of microbes that colonize the human body is far greater than the number of cells that make it up. In recent years, it has been shown that bacteria play an essential role in the body; in fact, they are essential for the maturation of the intestine, the development and control of the immune system, the development of the brain, the metabolism of macronutrients, the synthesis of vitamins, and the energy balance. Bacteria play an essential role in defense of their territory against the entry of other bacteria that may be pathogenic to health. Metchnikoff, about a century ago, invented probiotics, assuming that the use of certain bacteria could be beneficial to maintaining health. Bacteria colonize our body from birth and breastfeeding, using the bacterial flora of the mother by accessing newborns through the mouth. Antibiotic therapies in pregnancy or cesarean section prevent this flow of probiotics to infants and open the way for very important diseases, such as diabetes and obesity. The alterations of oral bacterial flora are responsible for numerous diseases of the oral cavity and the idea of the use of probiotics is leading the way to new therapeutic perspectives.

Effects of very-low-calorie diet on body composition, metabolic state, and genes expression: a randomized double-blind placebo-controlled trial.

OBJECTIVE: Very low-calorie diets (VLCDs, < 800 kcal day-1) and Ketogenic diet (KD) are generally used as part of integrated intervention, medical monitoring and a program of lifestyle modification, to improve a multitude of clinical states. The effect of three different very low calories KD (VLCKD), with (VLCKD1) or without (VLCKD2,3) synthetic amino acid replacement of the 50% protein intake, were analyzed after weight loss. PATIENTS AND METHODS: The clinical study used a cross-over randomized double-blind placebo-controlled trial. Obese subjects, who were eligible for the study, were randomly (R) divided into three groups: one intervention group (IG) and two control groups (CG1 and CG2). We comprehensively analyzed body composition, serum metabolites, superoxide dismutase (SOD1), nuclear factor kappa-light-chain-enhancer of activated B cells (NfKB), Chemokine (C-C Motif) Ligand 2 (CCL2) gene expression. RESULTS: After VLDKDs a significant decreased in BMI was observed. TBF (kg) significantly decrease after VLCKD1 and VLCKD3. After VLCKD2, a reduction of waist circumference (p = 0.02), FM L2-L5 (p < 0.05) was observed. After VLCKD1 reduction of IMAT (p = 0.00), LDL-C (p = 0.00) and HDL-C (p = 0.00) were observed. No significant changes of GH, ESR, and fibrinogen were highlighted. CRP (p = 0.02) reduced significantly after VLCKD3. Significant modulation of SOD1 expression (p = 0.009), CRP and decrease of glucose levels (p = 0.03) were obtained after VLCKD3. CONCLUSIONS: This is the first study that analyzes comprehensively body composition, metabolic profile, and inflammation and oxidative stress genes expression after VLCKD. Our results show the efficacy of VLCKD with synthetic aminoacidic protein replacement, for the reduction of cardiovascular risk, without the development of sarcopenia and activation of inflammatory and oxidative processes.

Soluble CD54 induces human endothelial cells ex vivo expansion useful for cardiovascular regeneration and tissue engineering application.

AIM: Consistent expansion of primary human endothelial cells in vitro is critical in the development of engineered tissue. A variety of complex culture media and techniques developed from different basal media have been reported with alternate success. Incongruous results are further confounded by donor-to-donor variability and cellular source of derivation. Our results demonstrate how to overcome these limitations using soluble CD54 (sCD54) as additive to conventional culture medium. METHODS AND RESULTS: Isolated primary fragment of different vessel types was expanded in Ham's F12 DMEM, enriched with growth factors, Fetal Calf Serum and conditioned medium of Human Umbilical Vein Endothelial Cells (HUVEC) collected at different passages. Cytokine content of culture media was analyzed in order to identify the soluble factors correlating with better proliferation profile. sCD54 was found to induce the in vitro expansion of human endothelial cells (HECs) independently from the vessels source and even in the absence of HUVEC-conditioned medium. The HECs cultivated in the presence of sCD54 (50 ng/ml), resulted positive for the expression of CD146 and negative for CD45, and lower fibroblast contamination. Cells were capable to proliferate with an S phase of 25%, to produce vascular endothelial growth factor, VEGF, (10 ng/ml) and to give origin to vessel-like tubule in vitro. CONCLUSION: Our results demonstrate that sCD54 is an essential factor for the in-vitro expansion of HECs without donor and vessel-source variability. Resulting primary cultures can be useful, for tissue engineering in regenerative medicine (e.g. artificial micro tissue generation, coating artificial heart valve etc.) and bio-nanotechnology applications.

Dental caries and childhood obesity: analysis of food intakes, lifestyle.

AIM: The aims of this cross-sectional statistical study were to evaluate the association between obesity and dental caries and to assess the impact of food intake, oral hygiene and lifestyle on the incidence of dental caries in obese paediatric patients, analysed by Dual X-ray Absorptiometry (DXA). MATERIALS AND METHODS: A sample of 96 healthy patients, aged between 6 and 11 years (mean age 8.58±1.43) was classified in relation to body composition assessment and McCarthy growth charts and cut- offs. Body composition analysis, to obtain body fat mass (FM) and body fat free mass (FFM) measurements, was determined by means of a DXA fan beam scanner. The subjects underwent dental examination to assess the dmft/DMFT, and completed a questionnaire on food intake, oral hygiene habits and lifestyle. The sample was subsequently subdivided into four groups: Group A (normal weight - caries-free), Group B (normal weight with caries), Group C (pre-obese/obese - caries-free), Group D (pre-obese/obese with caries). STATISTICS: The statistical analysis was performed using SPSS software (version 16; SPSS Inc., Chicago IL, USA). Spearman's correlation was performed to evaluate the correlation between dmft/DMFT and FM%. The chi-square test was performed to assess the categorical variables, while the non-parametric Kruskal Wallis test and the Mann Whitney test were employed for the quantitive variables. Statististical significance was set at a P-value of 0.05. RESULTS: The preobese-obese children had higher indexes of dental caries than normal weight subjects, both for deciduous teeth (dmft 2.5 ± 0.54 vs 1.4 ± 0.38; p=0.030) and permanent teeth (DMFT 2.8 ± 0.24 vs 1.93 ± 1.79; p=0.039). The correlations between dmft/DMFT indexes and body composition parameters were analysed and a significant correlation between dmft/DMFT indexes and FM% was observed (p=0.031 for dmft, p=0.022 for DMFT). According to the data recorded, there was no statistically significant difference between Groups A, B, C and D in terms of food intake between meals (p=0.436), frequency of starch intake limited to the main meals (p=0.867), home oral hygiene (p=0.905), dental hygiene performed at school (p=0.389), habit of eating after brushing teeth (p=0.196), participation in extracurricular sport activities (p=0.442) and educational level of parents: father (p=0.454), mother (p=0.978). In contrast, there was a statistically significant difference between Groups A, B, C and D in terms of intake of sugar-sweetened drinks (p=0.005), frequency of sugar intake limited to the main meals (p<0.001), frequency of food intake between meals (p=0.038) and sedentary lifestyle (p=0.012). Successive analysis revealed a statistically significant difference between Group A and D in terms of intake of sugar-sweetened drinks (p=0.001), frequency of sugar intake limited to the main meals (p=0.008), and frequency of food intake between meals (p=0.018), and between Group C and D in terms of frequency of sugar intake limited to the main meals (p<0.001), and frequency of food intake between meals (p=0.040). CONCLUSION: This study shows a direct association between dental caries and obesity evident from a correlation between prevalence of dental caries and FM%. The analysis of food intake, dmft/DMFT, FM%, measured by DXA, demonstrates that specific dietary habits (intake of sugar-sweetened drinks, frequency of sugar intake limited to main meals, frequency of food intake between meals) may be considered risk factors that are common to both dental caries and childhood obesity.

Effects of compounds acting on GABA(B) receptors in the pentylenetetrazole kindling model of epilepsy in mice.

The involvement of GABA(B) receptors in the behavioural and epileptic electrocortical discharges occurring in chemical kindling induced by repeated treatments with a subconvulsant dose of pentylenetetrazole (25 mg/kg i.p.) has been investigated in CD1 mice. Behavioural and electrocorticographic epileptic seizures following kindling induced by pentylenetetrazole (25 mg/kg i.p.) were attenuated or completely antagonized in a dose-dependent manner by the GABA(B) receptor agonist R-baclofen (2 and 6 mg/kg) whilst the GABA(B) receptor antagonist 3-amino-propyl-diethoxy-methyl-phosphinic acid (CGP 35348, 25, 50 or 100 mg/kg) and 3-[1-(S)-(3, 4-dichloro-phenyl-ethyl]amino-2-(S)-hydroxy-propyl-benzyl-phosphinic acid (CGP 55845A, 10 or 20 mg/kg) produced a more rapid development of kindling and an increase in behavioural and electrocorticographic epileptic changes. In addition, all GABA(B) receptor antagonists were able to induce an increase in Fos and Jun protein expression in pentylenetetrazole (25 mg/kg i.p.) treated mice whilst the GABA(B) receptor agonist R-baclofen (2 or 6 mg/kg) attenuated the expression of Fos and Jun protein, at cortical and limbic structures. In order to study the persistence of changes induced by pentylenetetrazole kindling, different groups of mice were rechallenged with a kindling stimulus 15 or 30 days after withdrawal from the last injection of vehicle+pentylenetetrazole, R-baclofen+pentylenetetrazole or GABA(B) receptor antagonists+pentylenetetrazole. The groups receiving GABA(B) receptor antagonists+pentylenetetrazole showed a higher incidence of seizures following the kindling stimulus than mice receiving vehicle+pentylenetetrazole whilst animals treated with R-baclofen were protected from the kindling stimulus. The different effects observed following repeated treatment with the GABA(B) receptor agonist and antagonist used revealed that GABA(B) receptors are able to affect the development of the epileptic kindling state induced by pentylenetetrazole.

Influence of D-cycloserine on the anticonvulsant activity of some antiepileptic drugs against audiogenic seizures in DBA/2 mice.

D-Cycloserine (DCS; 1-100 mg/kg, intraperitoneally (i.p.)) was able to antagonise the audiogenic seizures in DBA/2 mice in a dose-dependent manner. DCS, 2.5 mg/kg i.p. did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, but potentiated the anticonvulsant activity of carbamazepine, diazepam, felbamate, lamotrigine, phenytoin, phenobarbital and valproate against sound-induced seizures in DBA/2 mice. The degree of potentiation induced by DCS was greatest for diazepam, phenobarbital, phenytoin and valproate, less for carbamazepine and least for lamotrigine and felbamate. The increase in anticonvulsant activity was usually associated with a comparable increase in motor impairment. However, the therapeutic index of the combined treatment of the above drugs+DCS, was more favourable than the same drugs+saline with the exception of DCS+carbamazepine and DCS+lamotrigine. Since DCS did not significantly influence the total and free plasma levels of the anticonvulsant drugs studied, pharmacokinetic interactions, in terms of plasma levels, are not probable. The possibility that DCS can modify the clearance from the brain of the anticonvulsant drugs studied cannot be excluded. DCS did not significantly affect the hypothermic effects of the anticonvulsants tested. In conclusion, DCS potentiates the anticonvulsant action of some classical antiepileptic drugs, most notably diazepam, phenobarbital, phenytoin and valproate.

Topiramate potentiates the antiseizure activity of some anticonvulsants in DBA/2 mice.

Topiramate (1-50 mg/kg, intraperitoneally (i.p.)) was able to antagonize audiogenic seizures in DBA/2 mice in a dose-dependent manner. Topiramate at dose of 2.5 mg/kg i.p., which per se did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, potentiated the anticonvulsant activity of carbamazepine, diazepam, felbamate, lamotrigine, phenytoin, phenobarbital and valproate against sound-induced seizures in DBA/2 mice. The degree of potentiation induced by topiramate was greatest for diazepam, phenobarbital and valproate, less for lamotrigine and phenytoin and not significant for carbamazepine and felbamate. The increase in anticonvulsant activity was associated with a comparable increase in motor impairment. However, the therapeutic index of the combination of all drugs+topiramate was more favourable than that of antiepileptics+ saline, with the exception of carbamazepine or felbamate+topiramate. Since topiramate did not significantly influence the total and free plasma levels of the anticonvulsant drugs studied, we suggest that pharmacokinetic interactions, in terms of total or free plasma levels, are not probable. However, the possibility that topiramate can modify the clearance from the brain of the anticonvulsant drugs studied cannot be excluded. In addition, topiramate did not significantly affect the hypothermic effects of the anticonvulsants tested. In conclusion, topiramate showed an additive effect when administered in combination with some classical anticonvulsants, most notably diazepam, phenobarbital, lamotrigine, phenytoin and valproate.

Effects of interleukin-2 on various models of experimental epilepsy in DBA/2 mice.

The effects of interleukin-2 (IL-2) on various models of experimental epilepsy were studied after intracerebroventricular administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. Convulsions were induced by physical stimulus (sound of 109 dB. 12-16 kHz) or by chemical compounds (bicuculline, cephazolin or kainate). The present study demonstrated that human recombinant IL-2 (hr-IL-2) and mouse recombinant IL-2 (mr-IL-2) not only did not antagonize audiogenic seizures in DBA/2 mice but increased the incidence of seizures after the highest doses studied. In addition, hr-IL-2 and mr-IL-2 dose dependently facilitated sound-induced seizures at subthreshold sound exposure (83 dB). Pretreatment with monoclonal rat-antimouse IL-2 antibodies significantly affected the changes of occurrence of audiogenic seizures in DBA/2 mice induced by mr-IL-2. In addition, pretreatment with anti-IL-2 receptor monoclonal antibodies (anti-Tac) was able to completely antagonize or reduce the effects of IL-2 on audiogenic seizures. The effects of mr-IL-2 were also studied in two different models of epilepsy: the bicuculline and cephazolin models, due to impairment of GABAergic transmission, and the kainate model, due to an increase in excitatory amino acid transmission. In all models, mr-IL-2 demonstrated to facilitate the seizures induced by these chemoconvulsants. Since the proconvulsant properties of IL-2 were antagonized by specific monoclonal antibodies, we suggest that some epileptic phenomena may be linked to stimulation of IL-2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulatory effects on lactotrophs and crop-sac of interleukin-1 and interleukin-2 in pigeons (Columba livia).

The ultrastructural effects of human-recombinant interleukin-1 beta (IL-1 beta) and human-recombinant interleukin-2 (IL-2) on the crop-sac (the target organ for prolactin secretion in birds) and the anterior pituitary lactotrophs, were studied in pigeons (Columba livia). The intraventricular microinfusion of the two interleukins produced maximal crop-sac stimulation with milk-like secretion, as demonstrated by the observation of ultrastructural changes in the lactiferous areas through scanning and transmission electron microscopy of crop-sac mucosa. A marked activation of the anterior pituitary lactotrophs was also observed. Crop-sac and pituitary lactotrophs stimulatory effects were prevented by a previous intraventricular treatment with monoclonal antibodies for IL-1 beta and IL-2 receptors, but not by an intraperitoneal administration of naloxone. The present results show that interleukins possess in pigeons marked stimulatory effects on prolactin secretion and that these are mediated by specific receptors.

Neurotoxic effects induced by intracerebral and systemic injection of paraquat in rats.

1 The neurotoxic effects elicited by paraquat after systemic and intracerebral injection were studied in rats. 2 Intrahippocampal microinfusion of paraquat (0.1 mumol) produced behavioural stimulation and electrocortical (ECoG) excitation followed, at 24 h, by multifocal brain damage. Similarly, microinfusion of paraquat (0.2-0.4 mumol) into the locus coeruleus, substantia nigra or into the raphe nuclei, where noradrenergic, dopaminergic and serotonergic neurons are present, respectively, elicited potent excitotoxic effects (n = 6 rats per dose and area). A lower dose (0.01 mumol) of the herbicide or injection of the vehicle (1.0 microliter) did not produce any behavioural, ECoG or neurodegenerative effect. 3 After systemic administration, paraquat (20 mg kg-1 s.c.) evoked limbic motor seizures and ECoG epileptogenic discharges; in 10 out of 15 treated rats neuronal cell death was observed in the pyriform cortex, but not in other brain regions. A dose of 5 mg kg-1 was ineffective. 4 Among the regions of the brain studied, high concentrations of paraquat were detected in the pyriform cortex 24 h after systemic administration (5.0 and 20 mg kg-1 s.c.) lower levels being observed in the caudate nucleus. 5 In conclusion, paraquat, given systemically or intracerebrally in rats produces neurodegenerative effects.

Age-related alterations in cardiovascular responsiveness to clonidine infused into the nucleus tractus solitarii in rats.

The cardiovascular response to the unilateral injection of clonidine into the nucleus tractus solitarii in old compared to young rats was evaluated. In 3-month old rats clonidine (0.25, 0.5 and 1 microgram) injected into the nucleus tractus solitarii in anaesthetized rats produced a significant fall in blood pressure (BP) and a significant decrease in heart rate (HR). In contrast, in 12 month old rats the maximum fall in blood pressure and heart rate was significantly less than in young animals. In addition, in older rats (24 month old) clonidine, at the same or larger doses given into the nucleus tractus solitarii did not produce any significant change in the cardiovascular parameters studied. In conclusion, the present experiments provide evidence that during ageing there is a progressive decrease in the cardiovascular response to alpha 2-adrenoceptor stimulation in the nucleus tractus solitarii. In addition, it is conceivable that such a decrease and subsequently the lack in response may be related to a progressive decrease in the number and/or affinity of the specific alpha 2-adrenoceptor binding sites at this level.